Impact of Menopausal Hormone Therapy on Colorectal Cancer Risk

A Systematic Review

Livia Nakhostin; Aurelia Stadler; Petra Stute


Clin Endocrinol. 2021;95(3):390-397. 

In This Article

Material and Methods

Protocol registration

The study protocol was registered with the Open Science Framework (, and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) Guidelines for reporting was used.

Eligibility Criteria and Screening

Up to 9 February 2021, a systematic literature search was performed using the database Embase. Eligibility criteria were original articles with post-/perimenopausal participants providing endpoints regarding gastrointestinal cancer outcomes and use of systemic MHT (including observational studies, systematic reviews and meta-analyses) in the English language since 1990. Conference abstracts, editorials, letters or reviews were excluded. The search string of the database by keywords and Emtree terms including synonyms and subordinated terms is described in Table S1.

Initial search was up to 1 October 2018 and then updated until 9 February 2021 during the revision of the manuscript to guarantee actuality of results. Update search was performed by the search string of the initial search, except narrowing the outcome to risk of colorectal cancer. 1001 potentially relevant articles were identified, out of which 57 original studies and nine meta-analyses were deemed eligible for the final synthesis (see Figure 1). For the present review, only studies examining colorectal cancer were analysed. Titles and abstracts were screened for eligibility based on PICO criteria in Table 1. Exclusion criteria were 'no application of MHT', 'endpoint long-term endometrial safety and bleeding pattern', 'colon cancer as adverse event', 'bile duct cancer as adverse event' and 'GI-cancer no endpoint'. In case of uncertainty, the full-text articles were assessed. Selected full articles (especially meta-analyses and systematic reviews) were searched for secondary and consequently tertiary literature. Systematic reviews uncombined with meta-analyses were then excluded.

Figure 1.

Prisma flow diagram

Risk of Bias Assessment

For evaluating the risk of bias, the Newcastle-Ottawa scale was used for nonrandomized studies, the Cochrane risk of bias tool for randomized studies and the AMSTAR scale ratings for meta-analyses. The second author (AS) verified the assessments of the first author by reviewing a random sample.